Galactosemia and Amenorrhea in the Adolescent

Abstract

Hereditary galactosemia is a biochemical genetic disease due to a deficiency of galactose-1-phosphate uridyltransferase (GALT) enzyme activity (OMIM 606999). Acute manifestations occur in the neonatal period and are, with rare exceptions, related to lactose ingestion. They include poor feeding and growth, emesis, jaundice, liver disease, bleeding diathesis, anemia, renal tubulopathy, cataracts, encephalopathy and death from E. coli sepsis. Chronic manifestations, which also develop in prospectively treated patients, involve (a) the brain, resulting in delayed language acquisition, speech defects, and learning problems, and (b) the ovary, in the majority of females, producing hypergonadotropic hypogonadism. The serum FSH level is elevated in infancy/early childhood in many, but not all patients with a severe phenotype. There are few reports of patients with classic galactosemia having undergone pregnancy, labor, and delivery. The pathologic findings in the ovary, including a persistence of primordial follicles and streak gonads, have been variable. The etiology of primary ovarian insufficiency (POI) in galactosemia is unknown. Clinical surveillance includes screening for abnormalities in ovarian function at an early age. Treatment consists of estrogen/progesterone supplementation at the appropriate age. Reduced BMD has been reported. Future research is needed (1) to delineate the mechanisms behind reduced ovarian function in these young women; (2) to determine the timing of the lesion: prenatal, postnatal, and both pre- and postnatal; (3) to determine whether elevated galactose-1-phosphate is both necessary and sufficient to induce primary ovarian insufficiency; and (4) to understand the mechanism(s) behind the reduced BMD seen in children and adolescents with galactosemia.

Introduction to the Maastricht workshop: lessons from the past and new directions in galactosemia

“…Furthermore, these late-onset apparent diet-independent complications occurred even if diet therapy began on day 1 of life (Waggoner et al 1990;Hughes et al 2009). In addition to the above well known diet-independent complications (Nelson et al 1991;Schweitzer et al 1993;Guerrero et al 2000;Robertson et al 2000;Webb et al 2003;Gubbels et al 2008;Berry 2008;Potter et al 2008), we now know that additional complications include poor growth and/or short stature, reduced bone mineral density, deficits in personality construct, mood disorder, tremor, cerebellar ataxia and extrapyramidal movement disorders (Kaufman et al 1993;Rubio-Gozalbo et al 2002;Leslie 2003;Bosch 2006;Panis et al 2007). In some instances, discrete neurological, imaging and neuropathological findings have been recorded (Crome 1962;Huttenlocher et al 1970;Haberland et al 1971;Jan and Wilson 1973;Nelson et al 1992;Belman et al 1986;Bohles et al 1986;Koch et al 1992;Kaufman et al 1995;Ridel et al 2005;Hughes et al 2009).…”

Acne Tarda and Male-Pattern Baldness Unmasking Primary Ovarian Insufficiency: A Case and Review

“…In a recent cross-sectional, case-control study with 76 women, among them 43 with POI and 33 with normal menstrual cycles, an increase in low-grade chronic inflammation and insulin resistance was documented in patients with POI [22]. Furthermore, women with POI have traditional risk factors for diabetes mellitus, including lower levels of vitamin D and zinc and higher levels of copper, procalcitonin, high-sensitivity C-reactive protein, and homeostasis model of assessment-insulin resistance [23].…”

Disorders of ovarian function in childhood and adolescence: evolving needs of the growing child. An endocrine perspective

“…29,30 Questions regarding early ovum salvage are commonly raised. Parents may elect for attempted ovum salvage at an age at which informed consent is not possible or for a girl whose understanding may be significantly limited by intellectual disability induced by the underlying condition.…”