Danon Disease
Summary
Clinical characteristics.
Danon disease is a multisystem condition with predominant involvement of the heart, skeletal muscles, and retina, with overlying cognitive dysfunction. Males are typically more severely affected than females. Males usually present with childhood onset concentric hypertrophic cardiomyopathy that is progressive and often requires heart transplantation. Rarely, hypertrophic cardiomyopathy can evolve to resemble dilated cardiomyopathy. Most affected males also have cardiac conduction abnormalities. Skeletal muscle weakness may lead to delayed acquisition of motor milestones. Learning disability and intellectual disability, most often in the mild range, are common. Additionally, affected males can develop retinopathy with subsequent visual impairment. The clinical features in females are broader and more variable. Females are more likely to have dilated cardiomyopathy, with a smaller proportion requiring heart transplantation compared to affected males. Cardiac conduction abnormalities, skeletal muscle weakness, mild cognitive impairment, and pigmentary retinopathy are variably seen in affected females.
Diagnosis/testing.
The diagnosis of Danon disease is established in a proband (male or female) with suggestive findings and/or a hemizygous (in males) or a heterozygous (in females) pathogenic variant in LAMP2 identified by molecular genetic testing.
Management.
Treatment of manifestations: While the age of onset and progression of disease are typically later and slower in females, the management approach in males and females is similar. Standard treatment guidelines for hypertrophic cardiomyopathy and heart failure; consideration of ablation therapy in those with cardiac pre-excitation and arrhythmia; physical therapy for skeletal muscle weakness; standard treatment for developmental delay / intellectual disability; use of low vision aids for those with retinopathy.
Surveillance: Electrocardiography at least annually with echocardiography and cardiac MRI at least every one to two years; ambulatory arrhythmia monitoring as needed based on symptoms; annual assessment of strength and for neurologic changes; monitoring of developmental progress, educational needs, and behavior at each visit with formal developmental assessments every three to five years during childhood; ophthalmology evaluation at least every three to five years.
Agents/circumstances to avoid: Avoidance of dehydration or over-diuresis in those with heart failure; in the presence of significant cardiac hypertrophy with obstruction and/or symptomatic arrhythmia, consideration of instituting the guidelines for physical exertion for individuals with sarcomeric hypertrophic cardiomyopathy.
Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment and surveillance.
Pregnancy management: Management should be guided by the degree of overt disease in the pregnant woman and per guidelines for pregnant women with hypertrophic or dilated cardiomyopathy, depending on their condition.
Genetic counseling.
Danon disease is inherited in an X-linked manner. If the mother of the proband has a LAMP2 pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who have a pathogenic variant in LAMP2 will transmit the pathogenic variant to all of their daughters and none of their sons. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygous and may have features of Danon disease. Once the causative pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing for Danon disease for a pregnancy at increased risk are possible.
Diagnosis
Danon disease is a multisystem condition with predominant involvement of the heart, skeletal muscles, and retina, with overlying cognitive dysfunction. Formal clinical diagnostic criteria for Danon disease have not been established.
Suggestive Findings
Danon disease should be suspected in a male with the following clinical, supportive laboratory, electrophysiologic, imaging, and family history findings.
Clinical findings
- Cardiomyopathy that is predominantly hypertrophic and rapidly progressive
- Mild muscle weakness
- Retinopathy. The most detailed report of retinal findings to date is from a family with four males with Danon disease, two of whom had a classic cone-rod dystrophy [Thiadens et al 2012] including:
- Progressive visual impairment
- Severe color vision disturbances
- Fundus examination revealing a bull's eye maculopathy and diffuse loss of pigment in the retinal pigment epithelium (RPE)
- Electroretinogram revealing reduced photopic (cone) and scotopic (rod) responses
- Visual field testing revealing a central scotoma
- Optical coherence tomography revealing thinning of the retinal outer segments (rods and cones) and RPE
- Mild intellectual disability
Supportive laboratory findings
- Elevated creatine kinase (~5-fold increase)
- Elevated asparate aminotransferase (AST) (~7-fold increase) and alanine aminotransferase (ALT) (~6-fold increase) with preserved hepatic synthetic function
- Muscle biopsy (either skeletal or cardiac) demonstrating a relatively specific vacuolar myopathy on standard histology but best seen by electron microscopy; substantial fibrosis is often present.
Note: (1) Muscle biopsy is not required to make the diagnosis; (2) tissue staining demonstrating absence of the LAMP-2 protein can confirm the diagnosis, although this assay is not widely available on a clinical basis.
Electrophysiologic findings
- Severe cardiac hypertrophy with or without evidence of outflow obstruction
- Wolff-Parkinson-White syndrome with pre-excitation on surface electrocardiogram
- Ventricular arrhythmias and atrial tachyarrhythmias
Imaging. Late gadolinium enhancement on cardiac MRI
Family history of male relatives with severe hypertrophic cardiomyopathy or female relatives with either hypertrophic or dilated cardiomyopathy consistent with an X-linked inheritance pattern
Note: Absence of a family history of cardiomyopathy does not preclude the diagnosis.
Danon disease should be suspected in a female with the following clinical, suggestive laboratory, and family history findings.
Clinical findings
- Either dilated or hypertrophic cardiomyopathy
- Retinal changes reminiscent of, but not as severe as, those seen in affected males
Laboratory findings
- Normal or mildly increased creatine kinase
- Normal or mildly increased AST and ALT with preserved hepatic synthetic function
Family history of male relatives with more severe hypertrophic cardiomyopathy or female relatives with either hypertrophic or dilated cardiomyopathy consistent with an X-linked inheritance pattern
Note: Absence of a family history of cardiomyopathy does not preclude the diagnosis.
Establishing the Diagnosis
Male proband. The diagnosis of Danon disease is established in a male with suggestive findings by identification of a hemizygous pathogenic variant in LAMP2 on molecular genetic testing (see Table 1).
Female proband. The diagnosis of Danon disease is usually established in a female proband with cardiac pre-excitation and cardiomyopathy (either hypertrophic or dilated) by identification of a heterozygous pathogenic variant in LAMP2 on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (exome sequencing and genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of Danon disease is broad, individuals with the distinctive features described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of Danon disease has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
Option 1
When the phenotypic and laboratory findings suggest the diagnosis of Danon disease, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
- Single-gene testing. Sequence analysis of LAMP2 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. Note: Lack of amplification by PCR prior to sequence analysis can suggest a putative single-exon, multiexon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.
- A cardiomyopathy or myopathy multigene panel that includes LAMP2 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Option 2
When the diagnosis of Danon disease is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Table 1.
Molecular Genetic Testing Used in Danon Disease
| Gene 1 | Method | Proportion of Probands with a Pathogenic Variant 2 Detectable by Method |
|---|---|---|
| LAMP2 | Sequence analysis 3, 4 | ~95% 5 |
| Gene-targeted deletion/duplication analysis 6, 7 | ~5% 5 |
Dougu et al [2009], D'Souza et al [2014]
- 1.
See Table A. Genes and Databases for chromosome locus and protein.
- 2.
See Molecular Genetics for information on allelic variants detected in this gene.
- 3.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
- 4.
Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.
- 5.
D'Souza et al [2014]
- 6.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
- 7.
The vast majority of pathogenic variants reported to date are nonsense, frameshift, splicing, and small insertion-deletion variants. A minority of pathogenic variants are due to large gene deletions, duplications, or rearrangements.
Clinical Characteristics
Clinical Description
Danon disease is an X-linked condition in which males are often more severely affected than females. A total of 146 molecularly confirmed affected individuals (90 males and 56 females) with Danon disease have been reported in the literature and the information below summarizes the findings in these individuals [Brambatti et al 2019] and in others who did not undergo clinical genetic testing.
Table 2.
Features of Danon Disease
| Feature | % of Males w/Feature | % of Females w/Feature | Comment |
|---|---|---|---|
| Hypertrophic cardiomyopathy | 96% | 30%-70% | Cardiomyopathy in females, when present, is less likely to be hypertrophic than in males. |
| Dilated cardiomyopathy | 4% | 30%-50% | In males, dilated cardiomyopathy may develop later as hypertrophic cardiomyopathy progresses; this does not appear to be the case in females. |
| Cardiac conduction abnormalities | >80% | 60%-100% | |
| Skeletal muscle weakness | 80%-90% | 12%-50% | Typically not progressive in females |
| Intellectual disability (typically mild) | ~80% | ~10% | Intellectual disability is usually mild but can be of variable degree, particularly in females. |
| Retinopathy | ~20% | ~20% | The % of individuals w/visual impairment may be higher for both males & females, as formal ophthalmology examinations are not always reported. |
Males
Males with Danon disease often present with the triad of severe cardiomyopathy, skeletal myopathy, and mild intellectual disability. Penetrance for cardiomyopathy approaches 100% in males, with 80%-90% of affected individuals experiencing some degree of skeletal muscle weakness and more than 70% experiencing some degree of cognitive impairment [D'Souza et al 2014].
Cardiac. The most striking and apparent clinical findings involve childhood onset of cardiomyopathy, arrhythmias, and the progressive development of heart failure. Males are affected earlier (average age of first symptom 12.1 years) than females (average age of first symptom 19.0 years), although females show a wider phenotypic spectrum (see Females). Limited data are available on presenting clinical symptoms, although chest pain and palpitations have been reported as common symptoms at the time of diagnosis [Boucek et al 2011].
- Cardiomyopathy. The typical early cardiac finding is concentric hypertrophy with persevered ejection fraction and normal heart cavity dimensions.
- Hypertrophic cardiomyopathy is present in 70%-88% of affected males [Boucek et al 2011, Brambatti et al 2019].
- In contrast to many other forms of hypertrophic cardiomyopathy, progression to severe hypertrophy, heart failure, and an almost certain need for transplantation in the second and third decades of life is typically seen in Danon disease.
- Reported ages of cardiac transplantation and death in males are 33.7 and 34.5 years, respectively [Boucek et al 2011].
- In a minority of affected males the cardiac features evolve to resemble dilated cardiomyopathy [D'Souza et al 2014], although in rare affected males dilated cardiomyopathy may be the initial presentation without an apparent hypertrophic phase [López-Sainz et al 2019].
- Electrophysiology. Pre-excitation findings on ECG are present in more than 80% of affected males. Atrial and ventricular arrhythmias may also be detected.
- Arrhythmias may cause clinical symptoms of palpitations or syncope.
- Pre-excitation, including Wolff-Parkinson-White syndrome, is the most common finding on ECG [D'Souza et al 2014], seen in approximately 48% of males at presentation [Brambatti et al 2019].
- In some instances a pre-excitation, Wolff-Parkinson-White pattern on electrocardiography may precede overt cardiomyopathy.
- Cardiac imaging most commonly involves echocardiography.
- Left-ventricular outflow obstruction is present in some individuals on exercise testing.
- Increasingly, cardiac MRI is proving to be a useful tool to characterize hypertrophy and quantify the presence of late gadolinium enhancement as a measure of cardiac fibrosis.
Neuromuscular. Skeletal muscle myopathy most often presents as slowly progressive proximal muscle weakness in the neck, shoulders, and legs [D'Souza et al 2014]. Affected males have varying degrees of functional impairment due to muscle weakness and underlying deficits in muscle activation [Stevens-Lapsley et al 2010].
- Although progression may occur, weakness is not typically disabling and most men retain the ability to ambulate. Because of this, the rehabilitation outcomes for men who undergo cardiac transplantation are generally good, although profound muscle weakness after cardiac transplantation has been rarely described [D'Souza et al 2014, Brambatti et al 2019].
- Creatinine kinase (CK) levels are elevated in most males (mean 944 U/L) [Boucek et al 2011]. It is unknown if elevated CK levels are present in affected males at birth or if they slowly increase over time as the disease develops.
- Delayed motor milestones are reported in approximately 20% of affected males [Boucek et al 2011, Brambatti et al 2019]. These deficits have not been well described in terms of gross and fine motor impairment or ages of onset.
- Dysmetria unrelated to muscle weakness has rarely been reported [Lacoste-Collin et al 2002].
Cognitive delays and behavioral issues. Clinical cognitive issues (learning disability or intellectual disability) probably affect close to 100% of males but have not been well characterized. Intellectual disability, most often in the mild range, has been reported in about 80% of affected males. Speech and language delays are common. Most affected males are able to [D'Souza et al 2014]:
- Learn to read
- Have a job
- Live independently
- Take part in a relationship
Other neuropsychiatric issues that have been reported primarily in case reports or as part of small case series of affected individuals include [Hatz et al 2010, D'Souza et al 2014]:
- Attention deficit disorder
- Behavior problems
- Psychiatric issues (e.g., severe depression, psychosis)
Due to the small number of individuals reported with these particular features, it is unclear whether these issues are directly related to Danon disease.
Retinopathy. The retinopathy described in variable detail in earlier reports (see commentary by Brodie [2012]) appears to be consistent with the cone-rod dystrophy described by Thiadens et al [2012] (see also Suggestive Findings).
- The severity varies even among males in the same family [Schorderet et al 2007, Thiadens et al 2012].
- While details regarding rate of vision decline in males are not available in the limited number of published reports in Danon disease, Brambatti et al [2019] reported the risk of "vision abnormalities" from "retinopathy" as 10.9% in the 129 males and females on whom data were available.
Gastrointestinal. Gastrointestinal/hepatic disease is suspected in a majority of affected males [D'Souza et al 2014]. Features may include:
- Hepatomegaly
- Elevated liver enzymes without hepatic synthetic dysfunction; however in many instances the elevated transaminases are suspected to be of skeletal muscle origin.
Respiratory disease is present in about half of affected males, with shortness of breath, chest tightness, coughing, and/or wheezing being reported most frequently [D'Souza et al 2014]. Respiratory muscle insufficiency and airway disease have not been characterized in detail.
Females
Overall, the phenotypic spectrum in females appears to be broader and more variable [Brambatti et al 2019]. Females develop symptoms later than males and are more apt to have a cardiac-restricted phenotype. Onset of symptoms in females is about ten to 15 years later than in affected males, with average age of onset of first symptom 19.0 years, average age of cardiac transplant 33.7 years, and average age of death 34.6 years [D'Souza et al 2014]. The proportion of heterozygous females who have evidence of cardiomyopathy is reported to be between 61% and 100%, whereas 12%-50% of heterozygous females are reported to have some degree of skeletal muscle weakness, and between 6% and 47% have been reported to have some degree of cognitive issues [D'Souza et al 2014]. Although some females appear to be nearly as severely affected as typically affected males, the average age of diagnosis in females is reported to be 27.9 years.
Cardiac features predominate in females with a heterozygous pathogenic variant in LAMP2, although some have no discernable clinical features [Stevens-Lapsley et al 2010].
- Cardiomyopathy. Cardiomyopathy affects more than 70% of females, with dilated cardiomyopathy being present in 30%-50% of females and hypertrophic cardiomyopathy in the remaining [Boucek et al 2011, Brambatti et al 2019]. In most instances a dilated cardiomyopathy is the presenting finding and evidence of preceding hypertrophic cardiomyopathy (that then converted to a dilated phenotype) is lacking.Of the heterozygous females who develop cardiomyopathy, about 18% receive a cardiac transplantation, compared to almost all affected males [D'Souza et al 2014]. However, as most data reported are cross-sectional, the prevalence of heart transplant in females may rise with age.
- Electrophysiology. Conduction abnormalities have been reported in 60% to 100% of women with a heterozygous pathogenic variant in LAMP2 [D'Souza et al 2014, Brambatti et al 2019].
- Pre-excitation with Wolff-Parkinson-White is identified in 32% of females at presentation [Brambatti et al 2019].
- With time, however, the prevalence of cardiac disease in females approaches that of males, with one comprehensive study of published case reports noting a composite outcome (death, heart transplant, or ventricular assist device) occurring in 37% of males and 37% of females [Brambatti et al 2019].
- Cardiac imaging most commonly involves echocardiography. In females with cardiac hypertrophy, imaging modalities and findings are similar to those in males, although the findings may be less severe in females (see Males, Cardiac imaging).
Neuromuscular. Skeletal muscle weakness is reported in 12%-50% of females with a heterozygous pathogenic variant in LAMP2 and appears to be milder than that of males [Boucek et al 2011, Brambatti et al 2019].
- Skeletal muscle weakness is not known to be progressive.
- Some females with a heterozygous pathogenic variant in LAMP2 develop minimal clinical muscle abnormalities in the fourth decade as their only symptom [Stevens-Lapsley et al 2010].
- Creatinine kinase (CK) levels are usually normal in females (mean 106 U/L) [Boucek et al 2011].
Cognitive delays. Some form of intellectual impairment has been reported in between 6% and 47% of female patients. Details on the definition or degree of intellectual impairment are largely lacking. The authors' collective experience is that females with Danon disease generally do not meet a formal definition of intellectual disability as defined by an IQ <70.
Eye. Retinal findings in females that are similar to but milder than those observed in males have been reported [Prall et al 2006, Schorderet et al 2007, Taylor et al 2007, Brambatti et al 2019]. It is unclear if Danon disease leads to legal blindness in females or to what degree the ocular phenotypes are progressive. Ophthalmic findings include changes to the peripheral retinal pigment epithelium that could lead to:
- Near-loss of visible pigment
- Abnormal electroretinogram
- Impaired vision
Gastrointestinal and respiratory symptoms have been reported in females but are not well characterized to date (see information pertaining to Males).
Genotype-Phenotype Correlations
To date, no specific genotype-phenotype correlations for pathogenic loss-of-function variants have been confirmed.
A small number of pathogenic missense variants and pathogenic variants confined to exon 9B of the LAMP-2B protein isoform have been reported in association with mild or atypical phenotypes [Musumeci et al 2005, van der Kooi et al 2008, Hong et al 2012, D'Souza et al 2014]. In some cases the onset of cardiac features is later in males (e.g., after the 4th decade) and rare males have been reported without overt hypertrophic or dilated cardiomyopathies. Data convincingly showing a deficiency or functional abnormality of LAMP-2 protein have not been widely reported with variants in this genomic region.
Penetrance
The penetrance in Danon disease is age dependent and has not been well studied in the literature. Given the severity of the cardiac phenotype, the penetrance is estimated as high or nearly complete in males by the second decade. Females appear to also have a high cardiac penetrance that is later in onset compared to males.
Nomenclature
Outdated terms for Danon disease represented in the literature:
- X-linked vacuolar cardiomyopathy and myopathy
- Glycogen storage disease IIb
- X-Linked pseudoglycogenosis II
- Antopol disease
- Lysosomal glycogen storage disease without acid maltase deficiency
Prevalence
Danon disease is rare; measures of the general population prevalence are not known. Among individuals with hypertrophic cardiomyopathy (which has an overall prevalence of ~1:500 persons) the prevalence of those with a pathogenic LAMP2 variant has been reported as 1%-4% [Charron et al 2004, Yang et al 2005].
Differential Diagnosis
The disorders listed in Table 3 have cardiac and/or skeletal muscle findings that may be similar to those in Danon disease. However, unlike Danon disease, these disorders are not known to be associated with intellectual disability or retinal disease.
Table 3.
Selected Genes of Interest in the Differential Diagnosis of Danon Disease
| Gene(s) | Disorder | MOI | Cardiomyopathy | Skeletal Muscle |
|---|---|---|---|---|
| GAA | Pompe disease | AR | Severe early-onset hypertrophic cardiomyopathy | Rapidly progressive muscle weakness (infantile form only) |
| MYBPC3 MYBPC3 TNNI3 TNNT2 (>30 genes) 1 | Hypertrophic cardiomyopathy | AD | Hypertrophic cardiomyopathy | Normal |
| PRKAG2 | Familial Wolff-Parkinson White syndrome (OMIM 194200) 2 | AD |
| Normal |
| VMA21 | X-linked myopathy w/excessive autophagy 3 (OMIM 310440) | XL | Hypertrophic cardiomyopathy (mild) in a minority of cases |
|
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked
- 1.
Listed genes represent the most common genes known to be associated with hypertrophic cardiomyopathy. See Phenotypic Series: Familial Hypertrophic Cardiomyopathy for additional genes associated with this phenotype in OMIM.
- 2.
Mutation of PRKAG2 is also known to be associated with hypertrophic cardiomyopathy.
- 3.
X-linked myopathy w/excessive autophagy is also associated with scoliosis and has extraocular muscle involvement.
Management
Suggested treatment guidelines for Danon disease were reported by D'Souza et al [2014]; however, consensus management guidelines have not been published and evaluation and management is typically based on expert opinion. Although the age of onset and progression of disease are typically later and slower in females, the management approach in males and females is similar.
Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Danon disease, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended.
Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with Danon Disease
| System/Concern | Evaluation | Comment |
|---|---|---|
| Cardiac | Electrocardiography | To evaluate for hypertrophy, arrhythmia, & conduction abnormalities |
| Echocardiography | Incl evaluation for left-ventricular outflow tract obstruction | |
| Cardiac MRI | Late gadolinium enhancement indicates fibrosis & likely ↑ arrhythmia risk | |
| Cardiopulmonary exercise testing | Has not been formally studied in individuals w/Danon disease | |
| Brain natriuretic peptide level | As a baseline | |
| Neuromuscular | Neurologic examination for signs of muscle disease | |
| Development | Developmental assessment in males (& as indicated clinically in females) | To incl motor, adaptive, cognitive, & speech/language evaluation |
| Evaluation for early intervention/special education | ||
| Retinopathy | Retinal examination for evidence of cone-rod dystrophy | To incl:
|
| Gastrointestinal | Liver function tests 1 | To incl AST, ALT, & LDH |
| Miscellaneous/ Other | Consultation w/clinical geneticist &/or genetic counselor | To incl genetic counseling |
Adapted from D'Souza et al [2014]
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BCVA = best corrected Snellen visual acuity; ERG = electroretinogram; LDH = lactate dehydrogenase
- 1.
If results are strikingly abnormal, evaluation of liver synthetic function (e.g., total protein, albumin) and evaluation for other causes of abnormal liver function may be considered.
Treatment of Manifestations
Table 5.
Treatment of Manifestations in Individuals with Danon Disease
| Manifestation/ Concern |
|---|