Homozygosity for a Y/22 chromosome translocation: t(Y;22) (q12;p12/13).

A newborn girl, homozygous for a balanced Y/22 chromosome translocation is described. This unique karyotype was detected during prenatal chromosome studies in the first pregnancy of a 26-year-old woman. Amniocentesis was performed because of clinical evaluation of severe fetal growth retardation in the 28th week of gestation. The cytogenetic results were confirmed using a lymphocyte culture after birth in the 30th week. Subsequent chromosome studies of the parents were hampered by the fact that the pregnancy was thought to be the result of artificial insemination with donorsperm. Nevertheless both, consanguineous, parents were shown to be carriers of the same, singular, chromosome translocation and the spermdonor could be excluded from paternity by bloodgroup- and HLA studies. Distamycin-A-DAPI chromosome staining and DNA studies of the mother were used to confirm the involvement of the Y-chromosome in this translocation. The probanda is developing quite normally at the age of 21 months.

Early diagnosis of recessive X-linked ichthyosis: elevation of cholesterol sulfate levels in placental sulfatase deficiency before the onset of skin symptoms.

Children and adults with recessive X-linked ichthyosis have elevated levels of cholesterol sulfate, a substrate of the deficient enzyme microsomal sulfatase, in blood, erythrocyte membrane, and ichthyotic scale. We investigated cholesterol sulfate levels in patients with microsomal sulfatase deficiency before birth in amniotic fluid and in maternal plasma and erythrocytes, in cord blood (plasma and erythrocytes), and in plasma in the first month of life before and after onset of skin symptoms. Levels in amniotic fluid and cord blood were elevated. The plasma levels in the first month, before as well as after onset of skin symptoms, were within the range found in older patients with manifest skin symptoms.

Excretion of (sulfated) steroids in the urine and excretion of cholesterol sulfate in the feces of boys with recessive X-linked ichthyosis.

The excretion of sulfated steroids was investigated in the urine and feces of six boys aged 9 months to 7 years and 10 months who had recessive X-linked ichthyosis. Profiles of urinary total steroids as well as sulfated steroids were normal. Cholesterol sulfate excretion in the urine was not elevated. In the feces 2-20% of total cholesterol was cholesterol sulfate, whereas in the feces of 28 healthy children no cholesterol sulfate was demonstrable. In the 6 patients total cholesterol excretion (500-2,500 mumol/kg feces) was also elevated in comparison with the 28 healthy controls (150-700 mumol/kg feces, mean 365 mumol/kg feces).

Cholesterol sulphate in the microsomal sulphatase deficient placenta.

Placental sulphatase deficiency (PSD) and recessive X-linked ichthyosis (RXLI) are known as a nosological entity, due to deficiency of the enzyme, steroid sulphatase. Prior studies have demonstrated high urinary excretion and some accumulation of sulphated steroids prenatally, and of accumulation of cholesterol sulphate postnatally. This study was undertaken to investigate the level of cholesterol sulphate in the sulphatase deficient placenta. Whereas cholesterol sulphate levels are elevated in blood, erythrocyte membrane and stratum corneum of patients with RXLI, cholesterol sulphate content of four investigated sulphatase deficient placentas was normal in comparison to six normal male controls and four male controls with low oestrogen excretion in the third trimester of pregnancy but with normal placental sulphatase activity. The explanation for normal cholesterol sulphate content of sulphatase deficient placentas is unknown but may be due to placental transport, rapid metabolism to other sulphated steroids or age-related differences in residual enzyme activities.

Gas-chromatographic determination of cholesterol sulfate in plasma and erythrocytes, for the diagnosis of recessive X-linked ichthyosis.

We describe a rapid method for determining cholesterol sulfate in plasma and erythrocytes. After its single-step isolation by means of anion-exchange chromatography cholesterol sulfate is hydrolyzed, trimethylsilylated, and determined by gas chromatography with flame ionization detection. 5 beta-Cholestan-3 alpha-ol sulfate is used as internal standard. The method enables simultaneous determination of dehydroepiandrosterone sulfate in plasma. We applied it for the diagnosis of seven patients with recessive X-linked ichthyosis. Concentrations are given for plasma and erythrocytes from four unaffected relatives of patients with X-linked ichthyosis, a patient with placental sulfatase deficiency, two patients with other types of ichthyoses, and 20 controls. The method may also be of use for the rapid isolation of other organic sulfates from biological material, as illustrated by a comparison of gas chromatograms of urine from a normal pregnant woman and that from a patient with placental sulfatase deficiency.

Sex-linked ichthyosis and placental sulphatase C deficiency.

Ichthyosis was diagnosed in six boys born from pregnancies in which placental steroid sulphatase deficiency was present. In four cases the diagnosis of sex-linked ichthyosis was certain, in the other two the ichthyosis was probably of the sex-linked type. No arylsulphatase C activity could be demonstrated histochemically either in the epidermis of these boys, or in the epidermis of adults with sex-linked ichthyosis, whilst it was present in normal controls. In cultured skin fibroblasts steroid-sulphatase activity was extremely low. We conclude that deficiency of steroid sulphatase C or arylsulphatase C or a third functionally linked enzyme is an important factor in the pathogenesis of sex-linked ichthyosis.

X-linked ichthyosis and X-linked placental sulfatase deficiency: a disease entity. Histochemical observations.

The combined occurrence of X-linked steroid sulfatase deficiency of the placenta and X-linked ichthyosis is reported in 6 unrelated boys. Placental steroid sulfatase deficiency was diagnosed on the basis of a very low total estrogen excretion (6 cases), verified prenatally by the dehydroepiandrosterone sulfate (DHEAS) loading test in 4 cases and postnatally by clinical investigations (6 cases) and by biochemical investigations (5 cases). In addition, microsomal arylsulfatase C (MAS) could not be detected in the placental homogenate of the five cases investigated. Lysosomal arylsulfatases were within the normal range. All boys developed well except for X-linked ichthyosis. In the 5 cases investigated the skin biopsy showed the same MAS deficiency histochemically in the granular layer of the epidermis as in the trophoblast cells. The same holds true for the skin of carriers. Steroid sulfatase activity of cultured skin fibroblasts from the boys was almost nil (3 cases). The histochemical technique offers a practical approach in the scientific investigation of keratotic conditions.

X-linked icthyosis. A sulphatase deficiency.

In 3 pregnant women oestrogen excretion in the urine was very low. The pregnancies were otherwise uncomplicated and the 3 infants, boys, were normal at birth, but later developed ichthyosis of the X-linked inherited type. Histochemically, the placenta in each case showed deficiency in arylsulphatase-type C activity. In all three children the skin showed the same enzyme deficiency. In the skin of 9 other unrelated (adult) patients with proved X-linked inherited ichthyosis vulgaris, arylsulphatase C activity was deficient. Skin from 5 normal adults and 5 normal children showed arylsulphatase C activity to be present. It is concluded that a sulphatase deficiency is a factor in the causation of ichthyosis of the X-linked inherited type.