Hyperuricemia, Pulmonary Hypertension, Renal Failure, And Alkalosis Syndrome

A number sign (#) is used with this entry because of evidence that hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome (HUPRAS) is caused by homozygous mutation in the SARS2 gene (612804), which encodes mitochondrial seryl-tRNA synthetase, on chromosome 19q13.2.

Description

HUPRA syndrome is a severe autosomal recessive multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Affected individuals are born prematurely (summary by Belostotsky et al., 2011).

Clinical Features

Belostotsky et al. (2011) reported in detail 3 patients from 2 unrelated Palestinian families from the same village. All were born premature (27-34 weeks' gestation) and presented in infancy with failure to thrive. Laboratory studies showed renal failure associated with multiple electrolyte abnormalities, including hyperuricemia, hyponatremia, and hypomagnesemia, and all developed hypochloremic metabolic alkalosis. Renal biopsy of 1 patient showed dedifferentiated, atrophic tubules with thick basement membrane or denuded tubules; ultrastructural studies showed that the tubular epithelial cells contained markedly enlarged mitochondria with paracrystalline lesions, consistent with a mitochondrial cytopathy. All also developed pulmonary hypertension with evidence of ventricular hypertrophy. Additional features included anemia, thrombocytopenia, and leukopenia, diabetes mellitus, hypotonia, and global developmental delay. The disorder was progressive, and all 3 patients died before age 14 months.

Inheritance

HUPRA syndrome is an autosomal recessive disorder (Belostotsky et al., 2011).

Molecular Genetics

In an infant boy, born of nonconsanguineous Palestinian parents, with HUPRA syndrome, Belostotsky et al. (2011) identified a homozygous mutation in the SARS2 gene (D390G; 612804.0001). Within the extended family, in an infant girl with HUPRA syndrome, born of first-cousin Palestinian parents, the authors identified homozygosity for the same D390G mutation. A third infant with a similar disorder from an unrelated Palestinian family from the same village was also found to carry the same homozygous mutation.