Classical familial homocystinuria in an adult presenting as an isolated lens subluxation

Abstract

To report a case of late diagnosis of a classical familial homocystinuria based on an ophthalmologic examination. A 35-year-old male with Marfan-like phenotype complained of a progressive increase of myopia during the previous 2 years. Ophthalmologic exploration showed a bilateral subluxation of the lens with inferior and nasal displacement. Biochemical study detected a profile of increased amino acid levels (homocysteinemia) consistent with suspected homocystinuria. Vascular and skeletal studies ruled out Marfan syndrome. Response to treatment demonstrated B(6)-non-responsive homocystinuria. Molecular study showed compound heterozygous T353 N and D444 N mutations of the cystathionine beta-synthase (CBS) gene, and also a C667T homozygous mutation of the methylenetetrahydrofolate-reductase (MTHFR) gene. Family study showed classical homocystinuria in his father and sister, although they did not present any systemic or ocular features of the disease. Homocystinuria is a metabolic disease usually presenting at an early age as vascular, skeletal and neuropsychiatric abnormalities, as well as ectopia lentis. Our case is atypical because of the absence of thromboembolism and the mild phenotype, in spite of being B(6)-non-responsive, and the association of a rare compound heterozygous mutation of the CBS gene and also an homozygous mutation of the MTHFR gene. It is necessary to rule out homocystinuria in patients with ectopia lentis, even in the absence of systemic symptoms.

Novel Compound Heterozygous CBS Mutations Cause Homocystinuria in a Han Chinese Family

“…The method for mutation screening was performed as described previously 13 . Besides the variants in CBS, mutations in the MTHFR gene also have been reported to cause homocystinuria 14 15 . Therefore, the coding sequences of CBS (NM_000071.2) and MTHFR (NM_005957.4) were amplified by polymerase chain reaction (PCR) using a MyCycler thermo cycler (Bio-Rad, Hercules, CA).…”

Delayed diagnosis of homocystinuria presenting as bilateral congenital lens subluxation

“…Nevertheless, significant delays in diagnosis happen [6]. EL occurs in around 80% of patients and it is the most common involvement in homocystinuria [7,8]. About 70% of patients will develop EL by eight years of age, and 82% by the age of 10 [9].…”

“…Treatment from infancy with pyridoxine, folic acid, and betaine reduces cardiovascular risk by 80-90% [12]. To prevent thromboembolism, antiaggregant treatment with acetylsalicylic acid should also be considered in cases of immobilization or after surgery [8].…”

Acute psychosis in an adolescent with undiagnosed homocystinuria

“…Using blood methionine levels as a hallmark for diagnosis, CBS deficiency has been detected by newborn screening with an incidence rate ranging from 1:58,000 to 1:1, 000,000 of cases and an overall incidence rate of 1:344, 000 of cases [9,10]. Epidemiology data show a variability in the prevalence of different mutations: some mutations, such as c.833 T > C (p.I278T) or c.1105C > T (p.R369C), are frequently found in Caucasians and in several European countries, with heterozygous rates crossing between 0.5 and 1.5 % of the population, corresponding to an incidence of predicted homozygosis rate between 1:17, 800 and 1:264,000 [11][12][13][14]. The late occurrence of psychiatric symptoms has been reported in adults with homocystinuria [4,15,16].…”