Abstract
This paper reports the clinical and metabolic findings in two sibling sisters born with fetal hydrops and eventually found to have deficient S-adenosylhomocysteine hydrolase (AHCY) activity due to compound heterozygosity for two novel mutations, c.145C>T; p.Arg49Cys and c.257A>G; p.Asp86Gly. Clinically, the major abnormalities in addition to fetal hydrops (very likely due to impaired synthetic liver function) were severe hypotonia/myopathy, feeding problems, and respiratory failure. Metabolic abnormalities included elevated plasma S-adenosylhomocysteine, S-adenosylmethionine, and methionine, with hypoalbuminemia, coagulopathies, and serum transaminase elevation. The older sister died at age 25 days, but the definitive diagnosis was made only retrospectively. The underlying genetic abnormality was diagnosed in the second sister, but treatment by means of dietary methionine restriction and supplementation with phosphatidylcholine and creatine did not prevent her death at age 122 days. These cases extend the experience with AHCY deficiency in humans, based until now on only the four patients previously identified, and suggest that the deficiency in question may be a cause of fetal hydrops and developmental abnormalities of the brain.
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Abbreviations
- AdoHcy:
-
S-adenosylhomocysteine
- AdoMet:
-
S-adenosylmethionine
- AHCY:
-
S-adenosylhomocysteine hydrolase
- tHcy:
-
total homocysteine
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Acknowledgements
The authors thank Dr. Teodoro Bottiglieri for performing retrospectively the assays listed in Table 1 for day-of-life 30 and Dr. Neil Buist for advice on managing patient 2. This work was supported by grants 098-0000000-2463 (to OV) and 108-1081870-1885 (to IB) of the Ministry of Science, Education, and Sports, Republic of Croatia
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Communicated by: K. Michael Gibson
Competing interest: None declared.
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Grubbs, R., Vugrek, O., Deisch, J. et al. S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes. J Inherit Metab Dis 33, 705–713 (2010). https://doi.org/10.1007/s10545-010-9171-x
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DOI: https://doi.org/10.1007/s10545-010-9171-x